People having been exploring and studying the chronic subdural hematoma (CSDH) for more than a century, and the earliest study may be dated back to more than 150 years ago. It is documented that Virchow first studied the formation mechanism of the chronic subdural hematoma, and Virchow firstly depicted this disease and proposed the hypothesis that the inner dura matter inflammatory hemorrhage is the cause to the CSDH, that is, Pachymeningitis Theory. Afterwards, pathological examinations and electron microscopy and other series of studies have found that the chronic subdural hematoma capsule contains a large number of abnormal sinusoid lacunar. Since then, the subdural hematoma “newborn envelop repeated bleeding theory” is gradually concentrated by the academic attention.
In recent years, fundamental studies on the chronic subdural hematoma have identified that the disease is an inflammatory angiogenic disease, and thus view point has been increasingly accepted by the public. The levels of inflammatory cytokines IL-6, IL-8 and IL-10 in the hematoma fluid are significantly increased relative to the peripheral blood, the levels IL-6 and VEGF in the hematoma fluid of the recurrence patients are significantly increased relative to the non-recurrence patients, and the VEGF expression in the adventitia of the hematoma cavity is significantly increased. The levels of these cytokines are closely related to the recurrence of hematoma. At the same time, the researchers have also found that angiogenesis-related factors PIGF, VEGF, bFGF, MMP-2 and MMP-9 in the hematoma fluid are significantly increased, and Ang-1 and Ang-2mRNA promoting generation of vessels in the adventitia of the hematoma are increased. A decrease of the proportion thereof indicates an increase of generation of new vessels. The combination of the inflammatory factors and the angiogenic factors may be a key factor in the formation of CSDH.
It is well recognized that surgical treatment of the chronic subdural hematoma is the most effective treatment, especially in the treatment of the patients with large amounts of hematoma, obvious clinical symptoms and a midline shift greater than 5 mm. Through the surgical operation, intracranial hypertension and hernia may be quickly relieved. In addition to the surgical treatment, other conservative treatments of the chronic subdural hematoma mainly include: pure resting lying guard, intracranial pressure reduction by mannitol dehydration, anti-epileptic treatment, glucocorticoid therapy, angiotensin-converting enzyme inhibitor, and even radiation therapy.
In recent years, a large number of reports reveal studies on the treatment of chronic subdural hematoma using hormones. For example, in the year of 2005, Sun reported that 25 patients who were intolerant to the surgical operation and have complications were treated using dexamethasone for 21 days (4 mg/6 h), and finally 23 patients (84%) had a better prognosis. In addition, the recurrences are significantly reduced for the patients after they were continuous administered with dexamethasone (DXM) for 2 weeks upon the surgical operation. Likewise, a separate retrospective study by Dran and Berghause has demonstrated that the death risk of the group postoperatively administered with dexamethasone is reduced by 3 folds as compared with the group with no administration of dexamethasone, and perioperative administration of dexamethasone may reduce the postoperative recurrence. A perspective study using dexamethasone by Delgado-Lopez et al. has also proved that it is effective to treat the chronic subdural hematoma with hormone. In the year of 2014, a randomized double-blind controlled clinical trail (DRESH trail) carried out by a China-Austria multi-center planed to admit 820 patients, and the finally result of the study would further clarify whether perioperative administration of dexamethasone can reduce postoperative CSDH recurrence. A placebo-controlled trail has been carried out in an experimental group and a control group in Canada each involving 10 patients (registration number: NCT02362321), and the final result shows that 1 patient in the group of dexamethasone is transferred to the surgical treatment whereas 3 patients in the group of placebo are transferred to the surgical treatment. However, in the above trails, a large mount of hormones is used. The excessive use of dexamethasone may cause obesity, gastrointestinal damage and other steroid-related complications. Therefore, the hormone-related therapy has not been promoted, and most applications thereof are limited to surgery auxiliary medication.
Chinese Patent application No. 201210014181.4, entitled with “USE OF STATIN IN PREPARING DRUG FOR THE TREATMENT OF CHRONIC SUBDURAL HEMATOMA” has disclosed that the statin may obviously promote absorption of chronic hematoma, such that hematoma of some patients is absorbed through conservative treatment with drugs, thereby avoiding surgical treatment. However, this therapy takes long to come into effect, and it is almost sixth months, or at least one month, from the time the patients receive the treatment and the time the hematoma is absorbed, which gives confusion to some patients.